The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15

Abstract

The generation of new adipocytes from precursor cells (adipogenesis) has implications for systemic metabolism and is a commonly used model for studying the process of cell differentiation in vitro. Previous studies from us and others suggested that the peripheral circadian clock can influence adipogenesis in vitro, but the mechanisms driving this activity and the relevance for adipogenesis in vivo are unknown. Here we reveal that mouse adipocyte precursor cells (APCs) contain a circadian clock that oscillates in vivo. We expose context-specific features of the clock in APCs: expression of the canonical core clock component Per1 does not significantly oscillate, whereas the lesser-understood paralog Per3 has a prominent rhythm. We discovered that deletion of Per3 promotes adipogenesis in vivo by a clock output pathway in which PER3 and BMAL1 directly regulate Klf15 expression. These findings demonstrate that Per3 has a major role in the APC clock and regulates adipogenesis in vivo. The function of the peripheral circadian clock in adipocyte biology is unclear. Aggarwal et al. reveal that adipocyte precursor cells contain a circadian clock with context-specific components. In particular, the component Period 3 (Per3) has a prominent role in the adipocyte precursor cell clock and specifies an output pathway to Klf15 that regulates adipogenesis.